| Summary: | Pancreatic ductal adenocarcinoma has a heterogeneous genetic landscape, marked by frequent mutation of KRAS, CDKN2A, TP53, and SMAD4, resulting in poor responses to conventional therapeutic regimens. Over the past decade, increased understanding of the genetic underpinnings of this lethal cancer has yielded several different characterizations of pancreatic cancer subtypes. However, not all phenotypes and changes in pancreatic cancer can be explained by these findings. New insights on epigenetic modifications associated with pancreatic carcinogenesis have highlighted additional pathways, other than gene mutations, among which chromatin regulation plays a dominant role. Gene expression is highly regulated by subtle changes in chromatin configuration. The underlying mechanism is dominated by reversible post-translational histone modifications. In addition, there is growing evidence that different chromatin mechanisms interact with one another, contributing to the diversity of pancreatic carcinogenesis. This review highlights recent work characterizing chromatin regulatory mechanisms associated with pancreatic carcinogenesis as well as future directions of this emerging research.
|
|---|